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Abnormalities in serum biomarkers correlate with lower cardiac index in the Fontan population

Published online by Cambridge University Press:  05 July 2016

Bradley S. Marino ,
David J. Goldberg ,
Adam L. Dorfman ,
Eileen King ,
Heidi Kalkwarf ,
Babette S. Zemel ,
Margaret Smith ,
Jesse Pratt ,
Mark A. Fogel  and
Amanda J. Shillingford
...Show all authors
Bradley S. Marino*
Affiliation:
Department of Pediatrics, Division of Cardiology, Division of Critical Care Medicine, Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
David J. Goldberg
Affiliation:
Department of Pediatrics, Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania United States of America
Adam L. Dorfman
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, University of Michigan C.S. Mott Children’s Hospital, Ann Arbor, Michigan, United States of America
Eileen King
Affiliation:
Department of Pediatrics, Division of Biostatistics & Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Heidi Kalkwarf
Affiliation:
Department of Pediatrics, Division of General and Community Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Babette S. Zemel
Affiliation:
Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America
Margaret Smith
Affiliation:
Department of Pediatrics, Division of Cardiology, Division of Critical Care Medicine, Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Jesse Pratt
Affiliation:
Department of Pediatrics, Division of Biostatistics & Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Mark A. Fogel
Affiliation:
Department of Pediatrics, Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania United States of America
Amanda J. Shillingford
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, Children’s Hospital of Wisconsin, Milwaukee, Wisconsin, United States of America
Barbara J. Deal
Affiliation:
Department of Pediatrics, Division of Cardiology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois United States of America
Anitha S. John
Affiliation:
Department of Pediatrics, Division of Cardiology, The Mayo Clinic, Rochester, Minnesota, United States of America
Caren S. Goldberg
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, University of Michigan C.S. Mott Children’s Hospital, Ann Arbor, Michigan, United States of America
Timothy M. Hoffman
Affiliation:
Department of Pediatrics, Division of Cardiology, Nationwide Children’s Hospital, Columbus Ohio, United States of America
Marshall L. Jacobs
Affiliation:
Department of Pediatric and Congenital Heart Surgery, Cleveland Clinic, Cleveland, Ohio, United States of America
Asher Lisec
Affiliation:
Department of Pediatrics, Division of Cardiology, Division of Critical Care Medicine, Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Susan Finan
Affiliation:
Department of Pediatrics, Division of Cardiology, Division of Critical Care Medicine, Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Lazaros K. Kochilas
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, University of Minnesota Amplatz Children’s Hospital, Minneapolis, Minnesota, United States of America
Thomas W. Pawlowski
Affiliation:
Department of Pediatrics, Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania United States of America
Kathleen Campbell
Affiliation:
Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Clinton Joiner
Affiliation:
Department of Pediatrics, Division of Hematology/Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Stuart L. Goldstein
Affiliation:
Department of Pediatrics, Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America
Paul Stephens Jr
Affiliation:
Department of Pediatrics, Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania United States of America
Alvin J. Chin
Affiliation:
Department of Pediatrics, Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania United States of America
*
Correspondence to: B. S. Marino, MD, MPP, MSCE, Professor of Pediatrics and Medical Social Sciences, Northwestern University Feinberg School of Medicine, Heart Center Co-Director, Research and Academic Affairs, Divisions of Cardiology and Critical Care Medicine, Ann and Robert H. Lurie Children’s Hospital of Chicago, 225 East Chicago Avenue, Box 21, Chicago, IL 60611-2991, United States of America. Tel: +312 227 4373; Fax: +312 227 9640; E-mail: bradley.marino@northwestern.edu
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Abstract

Background

Fontan survivors have depressed cardiac index that worsens over time. Serum biomarker measurement is minimally invasive, rapid, widely available, and may be useful for serial monitoring. The purpose of this study was to identify biomarkers that correlate with lower cardiac index in Fontan patients.

Methods and results

This study was a multi-centre case series assessing the correlations between biomarkers and cardiac magnetic resonance-derived cardiac index in Fontan patients ⩾6 years of age with biochemical and haematopoietic biomarkers obtained ±12 months from cardiac magnetic resonance. Medical history and biomarker values were obtained by chart review. Spearman’s Rank correlation assessed associations between biomarker z-scores and cardiac index. Biomarkers with significant correlations had receiver operating characteristic curves and area under the curve estimated. In total, 97 cardiac magnetic resonances in 87 patients met inclusion criteria: median age at cardiac magnetic resonance was 15 (6–33) years. Significant correlations were found between cardiac index and total alkaline phosphatase (−0.26, p=0.04), estimated creatinine clearance (0.26, p=0.02), and mean corpuscular volume (−0.32, p<0.01). Area under the curve for the three individual biomarkers was 0.63–0.69. Area under the curve for the three-biomarker panel was 0.75. Comparison of cardiac index above and below the receiver operating characteristic curve-identified cut-off points revealed significant differences for each biomarker (p<0.01) and for the composite panel [median cardiac index for higher-risk group=2.17 L/minute/m2 versus lower-risk group=2.96 L/minute/m2, (p<0.01)].

Conclusions

Higher total alkaline phosphatase and mean corpuscular volume as well as lower estimated creatinine clearance identify Fontan patients with lower cardiac index. Using biomarkers to monitor haemodynamics and organ-specific effects warrants prospective investigation.

Keywords

Fontancardiac MRIbiomarkerscardiac index
Type
Original Articles
Information
Cardiology in the Young , Volume 27 , Issue 1 , January 2017 , pp. 59 - 68
Copyright
© Cambridge University Press 2015 

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